Risk factors for major gastrointestinal bleeding in the general population in Finland

Table 1 Baseline characteristics for participants with and without major gastrointestinal bleedings during follow-up

Baseline characteristics	GIB, n = 403	No GIB, n = 33105	Overall, n = 33508
Age at baseline, mean (SD)	56.0 (12.1)	46.8 (13.0)	46.9 (13.0)
Sex
Male	256 (63.5)	15768 (47.6)	16024 (47.8)
Female	147 (36.5)	17337 (52.4)	17484 (52.2)
Yr of enrollment, Q1
1987	45 (11.2)	5872 (17.7)	5917 (17.7)
1992	51 (12.7)	5371 (16.2)	5422 (16.2)
1997	126 (31.3)	7857 (23.7)	7983 (23.8)
2002	108 (26.8)	8155 (24.6)	8263 (24.7)
2007	73 (18.1)	5850 (17.7)	5923 (17.7)
Region1
West	163 (40.4)	12570 (38.0)	12733 (38.0)
East	240 (59.6)	20535 (62.0)	20775 (62.0)
Marital status
Married, cohabiting, or registered partnership	278 (69.0)	24391 (73.7)	24669 (73.6)
Single, separated, divorced, or widow	125 (31.0)	8623 (26.0)	8748 (26.1)
Missing	0 (0.0)	91 (0.3)	91 (0.3)
Occupation
Non-manual (office/studying)	102 (25.3)	15889 (48.0)	15991 (47.7)
Manual (factory/construction/farming/forestry)	62 (15.4)	6692 (20.2)	6754 (20.2)
Family/housewife/pensioner	191 (47.4)	8033 (24.3)	8224 (24.5)
Unemployed	37 (9.2)	2006 (6.1)	2043 (6.1)
Missing	11 (2.7)	485 (1.5)	496 (1.5)
Education in tertiles2
Low	128 (31.8)	10029 (30.3)	10157 (30.3)
Moderate	113 (28.0)	10735 (32.4)	10848 (32.4)
High	144 (35.7)	11619 (35.1)	11763 (35.1)
Missing	18 (4.5)	722 (2.2)	740 (2.2)
Smoking
Never	168 (41.7)	17381 (52.5)	17549 (52.4)
Ex-smoker	121 (30.0)	7028 (21.2)	7149 (21.3)
Smoker	105 (26.1)	8273 (25.0)	8378 (25.0)
Missing	9 (2.2)	423 (1.3)	432 (1.3)
Alcohol consumption in grams per week
Non-drinker	164 (40.7)	12548 (37.9)	12712 (37.9)
Mild (0.1 g to 36.9 g)	65 (16.1)	6835 (20.6)	6900 (20.6)
Moderate (37 g to 86.9 g)	54 (13.4)	5914 (17.9)	5968 (17.8)
Heavy (≥ 87g)	101 (25.1)	6879 (20.8)	6980 (20.8)
Missing	19 (4.7)	929 (2.8)	948 (2.8)
Coffee consumption per day, cups
0	38 (9.4)	2858 (8.6)	2896 (8.6)
1–5	267 (66.3)	20294 (61.3)	20561 (61.4)
6–10	86 (21.3)	9008 (27.2)	9094 (27.1)
> 10	4 (1.0)	637 (1.9)	641 (1.9)
Missing	8 (2.0)	308 (0.9)	316 (0.9)
Physical activity
Minimal to mild	335 (83.1)	25306 (76.4)	25641 (76.5)
Moderate to heavy	52 (12.9)	7095 (21.4)	7147 (21.3)
Missing	16 (4.0)	704 (2.1)	720 (2.1)
Body mass index in kg/m2, mean (SD)	28.3 (5.2)	26.6 (4.6)	26.6 (4.6)
Missing	10 (2.5)	389 (1.2)	399 (1.2)
Waist-hip ratio, mean (SD)	0.93 (0.1)	0.88 (0.1)	0.88 (0.1)
Missing	5 (1.2)	404 (1.2)	409 (1.2)
Systolic blood pressure in mm Hg, mean (SD)	141.0 (22)	136.0 (20)	136.0 (20)
Missing	2 (0.5)	268 (0.8)	270 (0.8)
Diastolic blood pressure in mm Hg, mean (SD)	83.5 (12.7)	81.0 (11.7)	81.0 (11.7)
Missing	2 (0.5)	271 (0.8)	273 (0.8)
Total cholesterol in mmol/L, mean (SD)	5.69 (1.09)	5.58 (1.12)	5.58 (1.12)
Missing	5 (1.2)	347 (1.0)	352 (1.1)
High density lipoprotein in mmol/L, mean (SD)	1.39 (0.44)	1.44 (0.38)	1.44 (0.38)
Missing	5 (1.2)	347 (1.0)	352 (1.1)
Gamma-glutamyl transferase in U/L, mean (SD)	59.5 (141)	31.2 (45.0)	31.5 (47.4)
Missing	5 (1.2)	356 (1.1)	361 (1.1)

¹West Finland includes Turku and Loimaa as well as Helsinki and Vantaa. East Finland includes North Karelia, North Savo, Oulu, and Lapland.

²Educational tertiles were calculated according to years of education and were specific to the birth cohorts.

Data are n (%), unless otherwise indicated. GIB: Gastrointestinal bleeding; SD: Standard deviation; IQR: Interquartile range.

Table 2 Medical history in participants with and without gastrointestinal bleeding

Comorbidities	GIB, n = 403	No GIB, n = 33105	Overall, n = 33508
Precursors of GIBs1
0	355 (88.1)	31621 (95.5)	31976 (95.4)
1	45 (11.2)	1399 (4.2)	1444 (4.3)
2	3 (0.7)	78.0 (0.2)	81.0 (0.2)
3	0 (0)	7.00 (0.0)	7.00 (0.0)
Any cancer	63 (15.6)	2421 (7.3)	2484 (7.4)
Any psychiatric disorders	104 (25.8)	4653 (14.1)	4757 (14.2)
Stroke including SAH	39 (9.7)	1239 (3.7)	1278 (3.8)
Venous thromboembolism	17 (4.2)	728 (2.2)	745 (2.2)
Ischemic heart disease	101 (25.1)	3433 (10.4)	3534 (10.5)
Valvular heart disease	23 (5.7)	689 (2.1)	712 (2.1)
Atrial fibrillation	55 (13.6)	1512 (4.6)	1567 (4.7)
Peripheral artery disease	23 (5.7)	553 (1.7)	576 (1.7)
Heart failure	76 (18.9)	1810 (5.5)	1886 (5.6)
High blood pressure	128 (31.8)	6572 (19.9)	6700 (20.0)
Osteoarthritis	20 (5.0)	2062 (6.2)	2082 (6.2)
Inflammatory connective tissue diseases	29 (7.2)	1458 (4.4)	1487 (4.4)
Diabetes2	52 (12.9)	2390 (7.2)	2442 (7.3)
COPD	24 (6.0)	638 (1.9)	662 (2.0)
Asthma	54 (13.4)	3828 (11.6)	3882 (11.6)
Liver disorder	29 (7.2)	389 (1.2)	418 (1.2)
Anemia	6 (1.5)	70 (0.2)	76 (0.2)

¹Includes conditions without gastrointestinal bleeding such as gastritis, intestinal diseases, esophageal varices, esophagitis, hemorrhoids, colitis, Crohn’s disease.

²Excluding gestational diabetes.

Data are n (%). GIB: Gastrointestinal bleeding; COPD: Chronic obstructive pulmonary disease; SAH: Sub-arachnoid hemorrhage.

Table 3 Multivariate analysis for the risk factors for major gastrointestinal bleeding

Variables	Univariate model, HR (95%CI)	Multivariate model, HR (95%CI)
Baseline age (10-yr increase)	1.83 (1.69–1.99)	1.62 (1.42–1.86)
Sex
Male	1	1
Female	0.51 (0.42–0.63)	0.83 (0.59–1.17)
Yr of enrollment
1987	1	1
1992	1.23 (0.83-1.84)	1.15 (0.74–1.79)
1997	2.10 (1.50–2.96)	1.36 (0.91–2.04)
2002	1.72 (1.21–2.43)	1.10 (0.72–1.68)
2007	1.66 (1.15–2.41)	0.90 (0.57–1.43)
Region1
West Finland	1	1
East Finland	0.90 (0.74–1.10)	0.96 (0.77–1.20)
Marital status
Married, cohabiting, or registered partnership	1	1
Single, separated, divorced, or widow	1.29 (1.04–1.59)	1.09 (0.86–1.38)
Occupation
Non-manual (office/studying)	1	1
Manual (factory/ construction/ farming/ forestry)	1.45 (1.06–1.98)	1.25 (0.88–1.78)
Family/ housewife/ pensioner	3.90 (3.06–4.95)	1.26 (0.90–1.75)
Unemployed	2.92 (2.00–4.25)	1.70 (1.11–2.59)
Education2
Low	1	1
Moderate	0.82 (0.64–1.06)	0.81 (0.62–1.06)
High	0.96 (0.76–1.22)	1.05 (0.80–1.38)
Smoking
Never	1	1
Ex-smoker	1.80 (1.43–2.28)	1.18 (0.90–1.53)
Smoker	1.34 (1.05–1.71)	1.30 (0.97–1.74)
Alcohol consumption in grams per week
Non-User	1	1
Mild (0.1 g to 36.9 g)	0.72 (0.54–0.96)	0.88 (0.66–1.19)
Moderate (37 g to 86.9 g)	0.69 (0.51–0.94)	0.76 (0.54–1.06)
Heavy (≥ 87 g)	1.13 (0.88–1.44)	1.02 (0.76–1.37)
Coffee consumption per day, cups
0	1	1
1–5	1.00 (0.71–1.40)	0.72 (0.50–1.02)
6–10	0.72 (0.49–1.06)	0.67 (0.46–0.99)
> 10	0.48 (0.17–1.33)	0.43 (0.23–0.81)
Physical activity
None to Mild	1	1
Moderate to Heavy	0.55 (0.41–0.73)	0.85 (0.62–1.16)
Body mass index standardized	1.38 (1.27–1.50)	1.15 (1.01–1.32)
Waist hip ratio standardized	1.70 (1.55–1.86)	1.18 (0.98–1.43)
Systolic blood pressure standardized	1.30 (1.19–1.42)	0.85 (0.76-0.96)
Diastolic blood pressure standardized	1.24 (1.13–1.37)	-
Total cholesterol standardized	1.10 (1.00–1.21)	0.94 (0.84–1.05)
High density lipoprotein standardized	0.86 (0.77–0.95)	-
Gamma-glutamyl transferase standardized	1.10 (1.08–1.12)	1.05 (1.02-1.09)
Precursors of GIB3
0	1	1
≥ 1	9.44 (7.65–11.65)	1.90 (1.37–2.63)
Any cancer	2.66 (2.03–3.48)	1.47 (1.10–1.97)
Any psychiatric disorders	2.21 (1.77–2.77)	1.32 (1.01–1.71)
Stroke including SAH	2.98 (2.14–4.15)	1.31 (0.90–1.90)
Venous thromboembolism	2.04 (1.26–3.32)	-
Ischemic heart disease	3.14 (2.51–3.94)	1.16 (0.87-1.55)
Valvular heart disease	2.91 (1.91–4.44)	1.40 (0.88-2.25)
Atrial fibrillation	3.46 (2.60–4.60)	1.05 (0.73–1.51)
Peripheral artery disease	3.94 (2.59–6.00)	1.39 (0.87–2.23)
Heart failure	4.35 (3.39–5.58)	1.46 (1.04–2.05)
High blood pressure	1.92 (1.55–2.36)	0.90 (0.69–1.17)
Osteoarthritis	0.78 (0.50–1.23)	0.39 (0.24–0.65)
Connective tissue diseases	1.72 (1.18–2.51)	-
Diabetes4	1.97 (1.47–2.64)	0.76 (0.54–1.08)
Chronic obstructive pulmonary disease	3.57 (2.36–5.39)	1.26 (0.77–2.06)
Asthma	1.19 (0.89–1.58)	0.80 (0.58–1.11)
Liver disorder	6.95 (4.76–10.15)	3.20 (2.06–4.97)
Anemia	7.16 (3.20–16.04)	1.52 (0.48–4.83)

¹West Finland includes Turku and Loimaa as well as Helsinki and Vantaa. East Finland includes North Karelia, North Savo, Oulu, and Lapland.

²Educational tertiles were calculated according to years of education and were specific to the birth cohorts.

³Includes conditions without gastrointestinal bleeding such as gastritis, intestinal diseases, esophageal varices, esophagitis, hemorrhoids, colitis, or Crohn’s disease.

⁴Excluding gestational diabetes.

‘-‘ indicates that the variable was not included in the final multivariate Cox model based on the results from LASSO.

CI: Confidence Interval; GIB: Gastrointestinal bleeding; HR: Hazard ratio; SAH: Subarachnoid hemorrhage.